IL45763A - Process for preparing cyclicdicarboximido-substituted phosphonothioates - Google Patents

Description

Process for preparing cyclicdicarboximido-suba tituted P osphonoth oates 45763/2 In Israel Patent No. 40,675, there Is described a process for preparing cycllcdlcarboxlmldo phosphonothloates corresponding to the formula S R_ I PI_ (alkoxy)2 wherein R represents phthallmldo, mono-methylphthalimldo, 4-cyclohexene-1 ,2-d1carboximido, or mono-methyl -4-cyclo-hexene-1 ,2-carboxlmido and the alkoxy groups contain from 1 to 4 carbon atoms, which comprises reacting a phosphoro-chlorldothloate corresponding to the formula S CI— P li— (alkoxy)2 with an N-alkal1 -metal cyclicdicarboxlmide corresponding to the formula R-Me, wherein Me represents sodium or potassium at a temperature of from 0°C to 100°C In the presence of a catalyst selected from aromatic tertiary amines and ring-nitrogen containing heteroaromatlc compounds and an Inert tertiary alcohol.

This invention relates to an improved method for preparing cyclicdicarboximido-substituted phosphonothioates. Cyclicdicarboximido-substituted phosphonate compounds and methods for their preparation as well as their utility as pesticides and as active toxicants in compositions for the control of insect, mite., helminth, plant, fungal and bacterial organisms are known. One method of preparation taught by the prior art basically entails the reaction of an N-alkali metal derivative of a eyeliedicarboximido compound with an 0, O-dialkylphosphorochloridothioate in the presence of an inert amido reaction medium such as, for example, N-methyl-2-pyrrolidone, dimethylformamide, hexamethylphosphor-amide, N-acetylmorpholine, or dimethylacetamide.

Another method known in the prior art for preparing the compounds involves reacting an alkali metal phosphoro-amidothioate of the formula (alkoxy) 2 metal with a cyclicdicarboxylic anhydride of the formula 0 0 wherein R' is hydrogen or a variety of other substituents, in the presence of an inert liquid reaction medium followed by the treatment of the product so produced with a ring-closing reactant such as phosphorus or sulfur based acid halides or an anhydride of an organic mono-, di-, or poly- While the above-described processes are effective to produce the compounds, they are not entirely satisfactory because of their low yield. The present invention provides a process for preparing cyclicdicarboximido phosphonothio- ates corresponding to the formula S R-P- (alkoxy) 2 (I) wherein R represents phthalimido, mono-methylphthalimido, 4-cyclohexene-l, 2-dicarboximido, or mono-methyl-4-cyclohexene-l, 2-carboximido, whereby high yields sufficient to warrant economical commercialization can be obtained.

The process of this invention comprises reacting a phosphorochlor idothioate of the formula S (alkoxy) 2 -P-Cl with an N-alkali metal salt of a cyclicdicarboximide reac-tant of the formula 0 0 0 wherein R' is hydrogen or methyl and Me is sodium or potassium in the presence of a 1- (alkyl) imidazole and an inert tertiary alcohol.

The reaction is carried out at a temperature of from 0 to 100°C, preferably 20 to 50°C.

In the present specification and claims, the term "alkoxy" refers to alkoxy radicals of from 1 to 4 carbon atoms, inclusive. Such radicals would be for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, secondary butoxy, and tertiary butoxy. The two alkoxy radicals may be the same or different.

The term "alkyl" refers to alkyl radicals of from 1 to 4 carbon atoms, inclusive. Such radicals would be, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, secondary butyl and tertiary butyl.

Representative compounds embraced by formula I and which may be prepared by the process of this invention include: 0, O-dimethyl phthalimidophosphonothioate; 0-ethyl 0-methyl phthalimidophosphonothioate; 0, 0-diethyl phthalimidophosphonothioate; 0, 0-di- -buty1 phtha1 midophosphonothioate ; 0-ethyl 0-isopropyl (4-cyclohexene-l, 2-dicar-boximido) phosphonothioate ; 0, 0-di-n-propyl phthalimidophosphonothioate ; O-secondary-butyl 0-methyl phthalimidophosphonothioate; 0, O-di-tertiary-butyl phthalimidophosphonothioate; 0-ethyl 0-n-propyl (4-cyclohexene-l, 2-dicarboxi-mido) phosphonothioate ; 0-ethyl 0-n-propyl phthalimidophosphonothioate; 0, O-dimethyl (4-methyl-4-cyclohexene-l, 2-dicarboxi-mido) phosphonothioate ; 0, 0-di-n-propyl (4-cyclohexene-l, 2-dicarboxijmido) -phosphonothioate ; 0, 0-dimethyl (4-cyclohexene-l, 2 -dicarboximido) -phosphonothioate ; 0, 0-diethy1 (4-methylphtha1imido) phosphonothioate ; 0, O-di-n-butyl (3-methylphthalimido) phosphonothi- : * ' oate ; 0, O-diisopropyl phthalimidophosphonothioate; 0, 0-dimethyl (3-methylphthalimido) phosphonothioate ; 0, 0-dimethyl (4-methylphthalimido) phosphonothioate; 0, 0-diethyl (3-methylphthalimido) phosphonothioate; 0, 0-diisobutyl phthalimidophosphonothioate; 0, 0-dimethyl (3-methyl-4-cyclohexene-l, 2-dicar-boximido) phosphonothioate ; and 0, 0-diethyl (4-methyl-4-cyclohexene-lj 2-dicarboxi-mido) hosphonothioate .

The critical features of the present process are the use of a 1- (alkyl) imidazole as a catalyst and the use of a tertiary alcohol as a solvent or reaction medium. The absence of either of these components drastically reduces the yield of the desired product.

The amount of the 1- (alkyl) imidazole employed usually is from 0.01 to 10 mole percent by v/eight based on the v/eight of the N-alkali metal cyclicdicarboximide re-actant and preferably is from 1 to 5 mole percent.

While the amount of the solvent employed is not critical it has been found desirable to employ the solvent in an amount of from 0.2 to 10 moles of the tertiary alcohol solvent per mole of the N-alkali metal cyclocdicar-boximide reactant. In addition to the use of the tertiary alcohol as a solvent, it has been found that a co-solvent system can be also employed. The co-solvents employed are inert solvents which do not interfere with the action of the catalyst and tertiary alcohol. The specific co-solvent employed is not critical and the only limitation as to the solvent is that it is inert under the reaction conditions ~ employed. Representative inert co-solvents include hydrocarbons such as, for example, heptane, hexane, benzene, xylene, cyclohexane, or petroleum ethers; halocarbons such as, for example, carbon tetrachloride; and halohydrocarbons such as, for example, chloroform or methylene chloride. When one of the above co-solvents is employed it is usually employed in an amount of from 0.5 to 20 moles of the co-solvent per mole of the tertiary alcohol.

Representative 1- (alkyl) imidazoles which can be employed in the present method include: l-methylimidazole, 1-ethylimidazole, 1-n-propylimidazole, 1-isopropylimidazole, 1-n-butylimidazole, 1-seci-butylimidazole and 1-t-butylimida-zole.

Representative tertiary alcohols useful as the solvent or reaction medium in the present process are the tertiary aliphatic alcohols including, for example, tertiary-butyl alcohol (most preferred) , tertiary-amyl alcohol, and 3-methyl-3-pentanol; and the tertiary aromatic alcohols such as, for example, triphenyl carbinol.

Representative phosphorochloridothioate reactants include 0,0-dimethyl phosphorochlor idothioate, 0,0-diethyl phosphorochlor idothioate, 0-secondary butyl 0-methyl phosphorochloridothioate, 0, 0-di-n-butyl phosphorochloridothio-ate, 0, 0-diisopropyl phosphorochloridothioate, 0-ethyl 0-methyl phosphorochlor idothioate, 0-ethyl 0-isopropyl phosphorochlor ithioate, 0, 0-di-n-propyl phosphorochloridothioate, 0, 0-di-tertiary-butyl phosphorochloridothioate, 0,0-diiso-butyl phosphorochloridothioate, and 0-tertiary-butyl 0-n-propyl phosphorochloridothioate.

Representative N-alkali metal cyclicdicarboximide reactants include the N-sodium and potassium derivatives of phthalimide, 3-methylphthalimide, 4-methylphthalimide, 4-cyclohexene-l, 2-dicarboximide, 3-methyl-4-cyclohexene-1, 2-dicarboximidej and 4-methyl-4-cyclohexene-li 2-dicarboximide.

The desirable results of the present invention are obtained by reacting the alkoxy phosphorochloridothioate reactant and the N-alkali metal cyclicdicarboximide reactant with agitation, in the presence of the tertiary alcohol solvent and the 1- (alky1) imidazole catalyst.

Upon completion of the reaction, the desired product can be separated from the reaction mixture by first quenching the reaction mixture, such as by pouring the re-action mixture into water, adding additional solvent to the mixture, followed by heating the mixture from 60° to 70 °C. The aqueous phase is separated, and the organic phase containing the crude product is washed with water and cooled to about 0°C. The product is recovered by conventional separatory techniques such as centrifugation, decantation, or solvent evaporation. The product can be further purified, if desired, by solvent recrystallization followed by drying.

If no co-solvent has been employed, the product can be separated by quenching the reaction medium with water and separating the crude product by filtration. The crude product can be further purified by dissolving it in one of the above-identified co-solvents, heating the mixture to reflux, followed by the removal of any insoluble material by hot filtration. The solvent-crude product mixture is cooled to about 0°C, and the product is recovered therefrom by conventional separatory techniques such as filtration, centrifugation, decantation, or solvent evaporation. The product can be further purified, if desired, by solvent recrystallization followed by drying.

The N-alkali metal derivatives of the cyclicdi-carboximido compounds employed as starting materials can be prepared by known procedures wherein a cyclicdicarboximido compound of the formula H-R is reacted with an alkali metal hydroxide, and the alkali metal derivative of the dicarboxi-mido compound is separated from the reaction mixture.

The dialkoxy phosphorochloridothioates employed as starting materials are known compounds and can be prepared by known procedures. For example, a thiophosphoryl chloride corresponding to the formula S Cl-P-Cl CI is reacted with a compound having the formula alkoxy-H or sim ltaneously or sequentially with two compounds having said formula alkoxy-H. Good results are obtained when employing the reactants in amounts which represent equimolecu-lar proportions. When both of the alkoxy-H reactants are to be the same, good results are obtained when employing two molecular proportions of such reactant and one molecular proportion of thiophosphoryl chloride.

The reaction is carried out in the presence of an acid binding agent such as, for example, an organic tertiary amine compound. Conveniently, the reaction is carried out in an inert organic liquid such as, for example, diethyl ether, benzene, carbon tetrachloride or methylene chloride, The following examples illustrate the practice ^ of the invention.

EXAMPLE 1 : 0,0-Diethyl phthalimidophosphonothioate To an agitating mixture comprising 187 pounds (2.53 pound moles) of tertiary-butyl alcohol and 563 pounds (6.53 pound moles) of hexane was added 330 pounds (1.78 pound moles) of potassium phthalimide and 6 pounds (0.073 pound mole; 4.1 mole percent based on potassium phthalimide) of 1-methylimidazole. This mixture was heated to 40°-45°C.i and thereafter 370 pounds (1.96 pound moles) of 0,0-diethyl phosphonochloridothioate was added over a period of about 2 hours. After a reaction period of 4 hours, the reaction mixture was quenched with water and additional hexane added. The mixture was heated to 60°-70°C. and the aqueous phase removed. The mixture was water washed for a total of 4 washes and cooled to 0°C. Crude 0,0-diethyl phthalimidophosphonothioate was recovered by centrif gation and the product purified by recrystallization from cold hexane and dried in a vacuum oven at 40 °C. The product which was re-covered in a yield of 85 percent of theoretical, melted at 81°-83°C. and was about 99 percent pure.

EXAMPLE 2 To an agitating mixture comprising 896 pounds (12.0 pound moles) of tertiary-butyl alcohol and 6 pounds of 1-methylimidazole (0.073 pound mole; 4.1 mole percent based on potassium phthalimide) was added 330 pounds (1.78 pound moles) of potassium phthalimide. This mixture was heated to 40°-45°C. and thereafter 370 pounds (1.96 pound moles) of 0,0-diethyl phosphorochloridothioate was added over a period of about 2 hours. After a reaction period of 4 hours, the reaction mixture was quenched with water and the crude 0,0-diethyl phthalimidophospho othioate product was recovered by filtration. The product was purified by dissolving it in 1850 pounds of hexane, and this mixture was heated to reflux and filtered hot to remove the insoluble by-products which formed. The filtrate was cooled to 0°C., and the desired purified product which crystallized upon cooling was recovered by centrifugation. The product was washed with cold hexane and dried in a vacuum oven at 40 °C. The product was about 99 percent pure and was obtained in a yield of about 85 percent of theoretical.

Claims (14)

THE CLAIMS DEFINING THE INVENTION ARE AS FOLLOWS: WHAT IS CLAIMEDfctfS:

1. A process for preparing cyclicdicarboximido phosphonothioates corresponding to the formula S R-P- (alkoxy) 2 wherein R represents phthalimido, mono-methylphthalimido, 4-cyclohexene-lj 2-dicarboximido or mono-methyl-4-cyclohexene-1, 2-carboximido which comprises reacting a phosphorochlorido-thioate corresponding to the formula ^ ^alkoxy Cl-P alkoxy with an N-alkali-metal cyclicdicarboximide corresponding to the formula 0 0 wherein R' represents hydrogen or methyl and Me represents sodium or potassium at a temperature of from 0°C. to 100°C in the presence of a 1- (alkyl) imidazole and an inert tertiary alcohol, each of said alkoxy and alkyl radicals containing from 1 to 4 carbon atoms.

2. A process as defined in Claim 1 wherein the temperature is in the range of from 20 °C. to 50 °C.

3. A process as defined in Claim 1 or 2 wherein the l-alkylimidazole is 1-methylimidazole.

4. A process as defined in any one of Claims 1 to 3 wherein the l-alkylimidazole is present in an amount of from 0.01 to 10 mole percent by weight based on the weight of the N-alkali metal cyclicdicarboximide.

5. A process as defined in any one of Claims 1 to 3 wherein the 1-alkylimidazole is present in an amount of from 1 to 5 mole percent by weight based on the weight of the N-alkali metal cyclicdicarboximide.

6. A process as defined in any one of Claims 1 to 5 wherein the tertiary alcohol is selected from tertiary amyl alcohol, 3-methyl-3-pentanol, and triphenyl carbinol.

7. A process as defined in any one of Claims 1 to 5 wherein the tertiary alcohol is tertiary butyl alcohol.

8. A process as defined in any one of Claims 1 to 7 wherein the tertiary alcohol is present in an amount of from 0.2 to 10 moles per mole of the N-alkali metal cyclicdicarboximide.

9. A process as defined in any one of Claims 1 to 8 wherein the reaction is carried out in the presence, additionally, of an inert hydrocarbon, halocarbon, or halo-hydrocarbon co-solvent.

10. A process as defined in Claim 9 wherein the co-solvent is selected from heptane, benzene, xylene, cyclohexane, carbon tetrachloride, chloroform, and methylene chloride.

11. A process as defined in Claim 9 wherein the co-solvent is hexane.

12. A process as defined in any one of Claims 9 to 11 wherein the co-solvent is present in an amount of from 0.5 to 20 moles per mole of the tertiary alcohol.

13. A process/for^ reparing a cyclicdicarboximide phosphonothioate substantially as described hereinbefore with reference to any one of the specific examples.

14. A cyclicdicarboximido phosphonothioate whenever produced by the process claimed in any one of the preceding claims. P.0. Box 33116 , Tel-Aviv Attorneys for Applicant